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Abstract Purpose To compare five pulmonary surfactant (PS) administration strategies for neonates with respiratory distress syndrome (RDS), including intubation-surfactant-extubation (InSurE), thin catheter administration, laryngeal mask airway (LMA), surfactant nebulization (SN), and usual care, with a particular emphasis on the comparison of the LMA and SN with other strategies. Methods We conducted a systematic search of MEDLINE, EMBASE, PUBMED, and Cochrane CENTRAL databases up to November 2023. Two authors independently conducted data extraction, and assessed bias using the Cochrane Risk of Bias Tool. Frequency-based random-effects network meta-analyses were executed. Results A total of 36 trials and 4035 infants were included in the analysis. LMA (OR: 0.20, 95%CI: 0.09 to 0.42) and Less Invasive Surfactant Administration (LISA) (OR: 0.17, 95%CI: 0.09 to 0.32) significantly reduced intubation rates compared to usual care. SN had a higher intubation rate compared to LISA (OR: 3.36, 95%CI: 1.46 to 7.71) and LMA (OR: 2.92, 95%CI: 1.10 to 7.71). LMA had a higher incidence of BPD compared to LISA (OR: 2.59, 95%CI: 1.21 to 5.54). SN ranked second to LISA in preventing BPD and death, but its efficacy decreased after excluding high-risk studies. SN and LMA had the lowest incidence of adverse events during administration.SN had the highest likelihood of secondary administration. Most results were rated as low or very low quality, with findings related to SN significantly impacted by high-risk trials. Conclusions The thin catheter strategy minimized intubation risk and showed a better composite effect in reducing both mortality and BPD incidence. SN and LMA each showed safety and some clinical benefits in the subpopulations where they were studied, but their efficacy needs further validation through high-quality studies. Registration This study was registered in PROSPERO (CRD42023463756).

Abstract Background At present, preterm infants with respiratory distress syndrome (RDS) in China present higher mortality and morbidity rates than those in high-income countries. The aim of this nationwide survey was to assess the clinical management of RDS in China. Methods A nationwide cross-sectional survey to assess adherence to RDS management recommendations was performed. One neonatologist per hospital was randomly selected. The primary outcome was the key care of RDS management. Results Among the 394 participating hospitals, 88·3% were birthing centres. The number of doctors and nurses per bed were 0·27 and 0·72, respectively. Antenatal corticosteroids (any dose) were administered to 90% of the women at risk of preterm birth at 32 weeks. T-piece resuscitators were available in 77·8% of delivery rooms (DRs) (tertiary hospitals: 82·5% vs. secondary hospitals: 63·0%, p

Abstract Background Microglial activation is one hallmark of Alzheimer disease (AD) neuropathology but the impact of the regional interplay of microglia cells in the brain is poorly understood. We hypothesized that microglial activation is regionally synchronized in the healthy brain but experiences regional desynchronization with ongoing neurodegenerative disease. We addressed the existence of a microglia connectome and investigated microglial desynchronization as an AD biomarker. Methods To validate the concept, we performed microglia depletion in mice to test whether interregional correlation coefficients (ICCs) of 18 kDa translocator protein (TSPO)-PET change when microglia are cleared. Next, we evaluated the influence of dysfunctional microglia and AD pathophysiology on TSPO-PET ICCs in the mouse brain, followed by translation to a human AD-continuum dataset. We correlated a personalized microglia desynchronization index with cognitive performance. Finally, we performed single-cell radiotracing (scRadiotracing) in mice to ensure the microglial source of the measured desynchronization. Results Microglia-depleted mice showed a strong ICC reduction in all brain compartments, indicating microglia-specific desynchronization. AD mouse models demonstrated significant reductions of microglial synchronicity, associated with increasing variability of cellular radiotracer uptake in pathologically altered brain regions. Humans within the AD-continuum indicated a stage-depended reduction of microglia synchronicity associated with cognitive decline. scRadiotracing in mice showed that the increased TSPO signal was attributed to microglia. Conclusion Using TSPO-PET imaging of mice with depleted microglia and scRadiotracing in an amyloid model, we provide first evidence that a microglia connectome can be assessed in the mouse brain. Microglia synchronicity is closely associated with cognitive decline in AD and could serve as an independent personalized biomarker for disease progression.

Sleep deprivation is a common public problem, and researchers speculated its neurophysiological mechanisms related to cortical excitatory and inhibitory activity. Recently, transcranial magnetic stimulation combined with electromyography (TMS-EMG) and electroencephalography (TMS-EEG) have been used to assess cortical excitability in sleep-deprived individuals, but the results were inconsistent. Therefore, we conducted a meta-analysis to summarize relevant TMS-evoked indices of excitability and inhibition for exploring the cortical effects of sleep deprivation. In TMS-EMG studies, short-interval cortical inhibition (SICI) significantly decreased in sleep-deprived subjects; while the intracortical facilitation (ICF), resting motor threshold (RMT), and cortical silent period (CSP) were not significant compared to healthy controls. In TMS-EEG studies, the amplitude and slope of TMS-evoked potential (TEP) increased in sleep-deprived subjects. This study indicated that cortical inhibition decreased following sleep deprivation based on the TMS-EMG results and cortical excitability enhanced in the TMS-EEG results, supporting the disturbance of cortical excitability in sleep-deprived individuals.

Background: Schizophrenia is associated with an increased risk of mortality and physical comorbidities, indicating a potentially accelerated frailty process in affected individuals. This study aimed to test association between schizophrenia and frailty using the frailty index based on laboratory markers (FI-Lab). Methods: A total of 600 patients with schizophrenia and 518 healthy controls, aged between 20 and 69 years were included in the present study. Frailty was assessed using the FI-Lab, incorporating routine laboratory markers, body mass index, and blood pressure measurements. FI-Lab for patients with schizophrenia and healthy controls was compared, with stratification by age group and sex. In addition, robust was defined as FI-Lab ≤ 0.12, pre-frail as 0.12–0.25, and frail as >0.25. Multiple linear regression analysis was used to test the association between schizophrenia and FI-Lab. Multinomial logistic regression was used to test the association between schizophrenia and frailty status. Spearman correlation analysis was performed to assess the relationship between the Positive and Negative Syndrome Scale (PANSS) scores and FI-Lab in schizophrenia patients. Results: Schizophrenia patients exhibited significantly higher FI-Lab than healthy controls across all age groups, indicating accelerated pace of frailty in schizophrenia patients. Schizophrenia was significantly associated with FI-Lab (β = 0.044, p = 0.004) in the adjusted model. Schizophrenia was significantly associated with both pre-frail status (OR = 2.26, 95% CI = 1.40−3.68, p = 0.001) and frail status (OR = 10.33, 95% CI = 5.65−19.93, p = 0.007) compared to robust status in the adjusted model. Additionally, a positive correlation between FI-Lab and PANSS scores suggests that more severe schizophrenia symptoms correlate with higher degree of frailty. Conclusion: These findings suggest that schizophrenia contributes to an increased risk of frailty. The FI-Lab provides a quantitative measure of frailty. This underscores the importance of integrating frailty considerations into the treatment and management of schizophrenia.

Abstract Preterm infants may need supplemental oxygen due to immature lungs. Regardless of the type of oxygen therapy used, bedside clinicians frequently adjust the FiO2 level. Automatic oxygen management is progressively developing as a viable alternative to these corrections. The purpose of this study is to compare the efficacy and safety of automated versus manual oxygen control in preterm infants receiving respiratory support. All the studies were searched from PubMed, Web of Science, Cochrane Library, Embase, CNKI, Wan Fang, VIP, and CBM on 7 May 2022. PICOS criteria were as follows: (P) participants were preterm infants receiving respiratory support; (I) intervention was automatic oxygen control; (C) comparator mode was manual oxygen control; (O) the primary outcome was the percentage of time within the target pulse oxygen saturation range; (S) randomized clinical trials. Sixteen studies were included in this meta‐analysis. The results showed that automated oxygen control can increase the percentage of time spent within the target SpO2 range while reducing the percentage of time spent above the target SpO2 range, the percentage time of hypoxemia, and manual FiO2 adjustments/hour. No significant difference was observed in the percentage of time spent below the target SpO2 range, incidence of bradycardia, and the mean SpO2 or mean FiO2 level. Automatic oxygen control can improve preterm infants' oxygen saturation, reduce periods of hypoxemia and the percentage of time spent above the target SpO2 range, and ease the workload of medical staff without affecting the mean FiO2 and mean SpO2 levels.

Background Non-invasive ventilation combined with pulmonary surfactant (PS) therapy is recognised as a method for treating neonatal respiratory distress syndrome (NRDS). Among the administration, methods of PS, INtubation–SURfactant–Extubation (InSurE) and less invasive surfactant administration (LISA) have been widely discussed.LISA technique prevents patients from exposure to invasive positive pressure ventilation (PPV), thus improving the long-term outcomes of the respiratory system, but it faces challenges in resource-limited areas due to complexity and cost. The InSurE technique remains prevalent due to its simplicity. The new dual-lumen tracheal tube (NDT) is designed with a 0.2 mm diameter pathway on the sidewall for continuous administration of PS under continuous PPV. The purpose of this study is to compare the safety and effectiveness of the NDT InSurE technique versus the LISA technique in non-invasive ventilation for premature infants with NRDS, and to explore the applicability of the NDT.Methods and analysis This is a multicentre randomised controlled trial, planned to recruit 132 premature infants who meet the inclusion criteria from January 2024 to December 2024. They will be randomly assigned to the InSurE group using the NDT (experimental group) and the LISA group. The study will be conducted in six tertiary neonatal intensive care units in Yunnan province. The primary outcome is the rate of mechanical ventilation within 72 hours after birth. Secondary outcomes include the procedure data and major complications of NRDS, also include respiratory infections within 12 months of corrected age.Discussion We assume that the NDT is not worse than the LISA catheter. Based on the characteristics of the NDT, continuous PPV during drug administration, we designed this study to compare the InSurE technique using the NDT with the LISA technique. We aim to explore more benefits of the NDT and confirm wider clinical applicability. It will provide more options for doctors when using the InSurE technique.Ethics and dissemination This study complies with the Declaration of Helsinki and was approved by the medical ethics committee of Kunming Children’s Hospital (approval number 2023-03-297-K01) and theoretical committee of Qujing Maternal and Child Health Hospital. At the end of the study, we will organise the data, complete the statistical analysis and present our research findings in the form of a paper.There is lack of comparative research on the NDT InSurE technique and LISA, making this study innovative. If the hypothesis is confirmed, clinicians will have an additional option when using PS, and it may even replace endotracheal tube in InSurE technique. The limited number of preterm infants planned for recruitment in the study may restrict stratified analyses based on gestational age, which could affect the broad applicability of the study results. The study is limited to preterm infants with a gestational age of less than 32 weeks, which means that the results may not be applicable to preterm infants with a larger gestational age or other patient populations.

BackgroundExisting literature indicates that Gestational diabetes mellitus (GDM) and maternal obesity disrupt the normal colonization of the neonatal gut microbiota alone. Still, the combined impact of GDM and excessive gestational weight gain (EGWG) on this process remains under explored. The association between gestational weight gain before/after GDM diagnosis and neonatal gut microbiota characteristics is also unclear.The purpose of this study is to conduct investigation and analysis on the above-mentioned issues, providing a basis for optimizing clinical management plans.MethodsThis study involved 98 mother-infant pairs categorized into GDM and non-GDM groups. The GDM group was further subdivided based on gestational weight gain (GWG) into normal (GDM+NGWG) and excessive (GDM+EGWG) weight gain groups. Neonatal stool samples were collected within 24 hours post-delivery for gut microbiota profiling through 16S rRNA gene sequencing. Statistical analyses explored correlations between total GWG/BMI gain and those before/after GDM diagnosis (t-GWG/GBG; b-GWG/GBG; a-GWG/GBG) with key bacterial taxa.ResultsNotable genus-level changes included enrichment of Escherichia and Klebsiella, and depletion of Bacteroides, Bifidobacterium, Coprococcus, Ruminococcus among GDM-Total and GDM+EGWG groups compared to non-GDM. Further,LEfSe analysis identified 30 differential bacteria taxa between GDM-Total and healthy control groups, which increased to 38 between GDM+EGWG and non-GDM groups, highlighting more pronounced microbial shifts associated with EGWG. Clostridium was negatively correlated with t-GWG and newborn birth weight; The Coriobacteriaceae showed a negative correlation with t-GWG, t-GBG, and a-GBG. Additionally,Collinsella exhibited negative correlations with t-GBG and a-GBG.ConclusionThis study has identified that the presence of EGWG in GDM mothers further exacerbated neonatal gut microbial perturbations. Total GWG/GBG and those after the diagnosis of GDM were negatively correlated with the abundance of neonatal gut Clostridium, Coriobacteriaceae, and Collinsella. These findings provide new insights for precise prevention and management of GDM.

Abstract DSR2, a Sir2 domain-containing protein, protects bacteria from phage infection by hydrolyzing NAD+. The enzymatic activity of DSR2 is triggered by the SPR phage tail tube protein (TTP), while suppressed by the SPbeta phage-encoded DSAD1 protein, enabling phages to evade the host defense. However, the molecular mechanisms of activation and inhibition of DSR2 remain elusive. Here, we report the cryo-EM structures of apo DSR2, DSR2-TTP-NAD+ and DSR2-DSAD1 complexes. DSR2 assembles into a head-to-head tetramer mediated by its Sir2 domain. The C-terminal helical regions of DSR2 constitute four partner-binding cavities with opened and closed conformation. Two TTP molecules bind to two of the four C-terminal cavities, inducing conformational change of Sir2 domain to activate DSR2. Furthermore, DSAD1 competes with the activator for binding to the C-terminal cavity of DSR2, effectively suppressing its enzymatic activity. Our results provide the mechanistic insights into the DSR2-mediated anti-phage defense system and DSAD1-dependent phage immune evasion.

Abstract Background Flea bites could trigger a series of complex molecular responses in the host. However, our understanding of the responses at the molecular level is still relatively limited. This study quantifies the changes in gene expression in mice after flea bites by RNA sequencing (RNA-seq) from their spleens, revealing the potential biological effects of host response to flea bites. Methods RNA-seq was used for transcriptome analysis to screen for differentially expressed genes (DEGs) between the control mice group and the flea bite mice group. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed on DEGs. Protein–protein interaction (PPI) network analysis on DEGs related to immune processes was performed. Finally, we randomly selected several genes from the screened DEGs to validate the results from the transcriptome data by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR). Results A total of 521 DEGs were identified, including 277 upregulated and 244 downregulated. There were 258 GO terms significantly enriched by upregulated DEGs and 419 GO terms significantly enriched by downregulated DEGs. Among the upregulated DEGs, 22 GO terms were associated with immune cells (e.g., B cells and T cells) and immune regulatory processes, while among the downregulated DEGs, 58 GO terms were associated with immune cells and immune regulatory processes. Through PPI analysis, we found that CD40 molecules with significantly downregulated expression levels after flea bites may play an important role in host immune regulation. Through KEGG pathway enrichment analysis, a total of 26 significantly enriched KEGG pathways were identified. The RT-qPCR analysis results indicated that the transcriptome sequencing results were reliable. Conclusions Through in-depth analysis of transcriptome changes in mice caused by flea bites, we revealed that flea bites could stimulate a series of biological and immunological responses in mice. These findings not only provided a deeper understanding of the impact of flea bites on the host but also provided a basis for further research on the interaction between ectoparasites and the host. We believe that digging deeper into the significance of these transcriptome changes will help reveal more about the adaptive response of the host to ectoparasites. Graphical Abstract

Cadmium (Cd) contamination of soil threatens human health, food security, and ecosystem sustainability. The in situ stabilization of Cd has been recognized as a potentially economical technology for the remediation of Cd-contaminated soil. Recently, biochar (BC) and activated carbon (AC) have received widespread attention as eco-friendly soil amendments that are more beneficial for plant growth, soil health, and remediation of contaminated soil. An experiment was performed in a paddy field to investigate the effects of two different types of BC (maize straw biochar and bamboo biochar) and AC (coconut shell activated carbon) in combination with rape organic fertilizer (R), calcium magnesium phosphate fertilizer (P), and fulvic acid (F), respectively, on soil Cd immobilization, Cd accumulation in rice, and yield. The results indicated that the BC/AC-based amendments reduced soil bioavailable Cd (DTPA-Cd) and brown rice Cd by 9.58%–27.06% and 19.30%–71.77%, respectively. The transformation of exchangeable Cd (Ex-Cd) to carbonate-bound Cd (Ca-Cd), Fe-Mn oxide bond (Ox-Cd), and residual (Re-Cd) in soil accounted for the mitigation of Cd uptake and enrichment by rice. Additionally, BC-/AC-based amendments altered soil physicochemical properties, which significantly increased the soil pH and cation exchange capacity (CEC), total nitrogen (TN), total phosphorus (TP), soil organic carbon (SOC), and dissolved organic carbon (DOC), directly promoting soil health. All BC-/AC-based amendments significantly increased FeIMP and MnIMP concentrations by 47.31%–160.34% and 25.72%–73.09% in the Fe/Mn plaque (IMP), respectively. Maize straw and bamboo biochar-based amendments significantly increased rice yield by 10.46%–20.41% and 9.94%–16.17%, respectively, while coconut shell-activated carbon severely reduced rice yield by 65.06%–77.14%. The correlation analysis revealed that leaf Cd and IMP primarily controlled Cd uptake by rice, and soil pH, Eh, CEC, SOC, IMP, and TP influenced DTPA-Cd in soil. This field study demonstrated that maize straw and bamboo biochar-based amendments not only reduced soil DTPA-Cd in paddy fields but also decreased the accumulation of Cd in brown rice, as well as improved rice yield, which has potential application in Cd-contaminated agriculture fields. Coconut shell-activated carbon severely decreased rice yields, which is not appropriate for rice production.

Background: Traffic-related air pollution (TRAP) is a major contributor to urban pollution and varies sharply at the street level, posing a challenge for air quality modeling. Traditional land use regression models combined with data from fixed monitoring stations may be unable to predict and characterize fine-scale TRAP, especially in complex urban environments influenced by various features. This study aims to estimate fine-scale (50 m) concentrations of nitrogen oxides (NO and NO₂) in Hong Kong using a deep learning (DL) structured model. Methods: We collected data from mobile air quality sensors on buses and crowd-sourced Google real-time traffic status as a proxy for real-time traffic emissions. Our DL model was compared with existing machine learning models to assess performance improvements. Using an interpretable machine learning method, we hierarchically evaluated the global, local, and interaction effects for different features. Results: Our DL model outperformed existing machine learning models, achieving R2 values of 0.72 for NO and 0.69 for NO₂. The incorporation of traffic status as a key predictor improved model performance by 9% to 17%. The interpretable machine learning method revealed the importance of traffic-related features and their pairwise interactions. Conclusion: The results indicate that traffic-related features significantly contribute to TRAP and provide insights and guidance for urban planning. By incorporating crowd-sourced Google traffic information, we assessed traffic abatement scenarios that could inform targeted strategies for improving urban air quality.

Abstract Ropivacaine is a commonly used local anesthetic for brachial plexus blocks in children, but the minimum effective dose of ropivacaine for interscalene brachial plexus blocks has not been reported. The aim of this study was to determine the 90% minimum effective concentration (MEC90) of ropivacaine for an ultrasound‐guided interscalene brachial plexus block (ISB). A total of 155 patients, aged from 1 to 10 years, underwent unilateral surgical procedures on areas of the upper extremity not innervated by the ulnar nerve. The biased coin design up‐and‐down sequential method (BCD‐UMD) was used to determine the MEC90 of ropivacaine for ultrasound‐guided ISB. In our study, the initial concentration of ropivacaine was 0.07% in the toddler group and 0.09% in the preschool and school‐age groups. During the trial, the concentration of ropivacaine for each subsequent patient was determined by the blocking effect of the previous patient. In case of failure, the concentration for the next patient was increased by 0.01%. Otherwise, the concentration was either decreased by 0.01%, with a probability of 0.11, or kept the same, with a probability of 0.89. Overall, the MEC90 of ropivacaine was 0.104% (95% confidence interval (CI), 0.070%–0.106%) in the toddler group, 0.114% (95% CI, 0.090%–0.117%) in the preschool group, and 0.133% (95% CI, 0.099%–0.136%) in the school‐age group. No adverse events occurred. Our study showed that lower concentrations of ropivacaine could provide effective nerve blocks and reduce the risk of local anesthetics.

In order to timely understand the research status and hot spots as well as the development trends of photodynamic sterilization worldwide, this paper adoptes bibliometrics method to analyze the research literatures in the filed of photodynamic sterilization which is collected through the core database of Web of Science from 2002 to 2022, aiming to provide references for researchers in related research fields. Meanwhile, the visualization analysis of different countries and regions, institutions and authors are carried out by the Citespace software, the cluster analysis and emergence analysis of the keywords in the field of photodynamic sterilization research are performed. According to the analysis, the selection and transformation of photosensitizers, the selection and optimization of light sources, and the extension of food shelf life are the research fields of photodynamic sterilization technology in the field of food. In addition, photodynamic combines with other cold sterilization technologies to enhance sterilization effect will also be a promising research field in the coming future.

Abstract Atypical antipsychotics (AAPs) are primary medications for schizophrenia (SZ). However, their use is frequently associated with the development of adverse metabolic effects, and the mechanisms behind these negative effects remain inadequately elucidated. To investigate the role of macrophage migration inhibitory factor (MIF) in regulating antipsychotic-induced metabolic abnormalities, between 2017 and 2020, a cross-sectional study was conducted, involving 142 healthy individuals and 388 SZ patients undergoing treatment with either typical antipsychotic (TAP) or AAP medications. Symptoms of SZ patients were evaluated using the Positive and Negative Syndrome Scale (PANSS), and measurements of metabolic indices and plasma MIF levels were performed on all individuals. A significant increase in plasma MIF levels was observed in groups receiving five major AAP monotherapies in comparison to healthy controls (all p 0.05). Elevated plasma MIF levels displayed a notable correlation with insulin resistance (β = 0.024, p = 0.020), as well as with the levels of triglycerides (β = 0.019, p = 0.001) and total cholesterol (β = 0.012, p = 0.038) in the groups receiving AAPs. However, while the TAP group also displayed certain metabolic dysfunction compared to healthy controls, no significant association was evident with plasma MIF levels (all p > 0.05). In conclusion, plasma MIF levels exhibit a distinctive correlation with metabolic abnormalities triggered by AAPs. Hence, there is potential for further development of MIF as a distinctive marker for monitoring adverse metabolic effects induced by AAPs in clinical settings.

Abstract Emerging tumor immunotherapy methods encompass bispecific antibodies (BSABs), immune checkpoint inhibitors (ICIs), and adoptive cell immunotherapy. BSABs belong to the antibody family that can specifically recognize two different antigens or epitopes on the same antigen. These antibodies demonstrate superior clinical efficacy than monoclonal antibodies, indicating their role as a promising tumor immunotherapy option. Immune checkpoints are also important in tumor immunotherapy. Programmed cell death protein-1 (PD-1) is a widely acknowledged immune checkpoint target with effective anti-tumor activity. PD-1 inhibitors have demonstrated notable therapeutic efficacy in treating hematological and solid tumors; however, more than 50% of patients undergoing this treatment exhibit a poor response. However, ICI-based combination therapies (ICI combination therapies) have been demonstrated to synergistically increase anti-tumor effects and immune response rates. In this review, we compare the clinical efficacy and side effects of BSABs and ICI combination therapies in real-world tumor immunotherapy, aiming to provide evidence-based approaches for clinical research and personalized tumor diagnosis and treatment.

In this paper, the microstructure and tensile mechanical properties of Mg-8.5Gd-4.5Y-0.8Zn-0.4Zr rare-earth (RE) magnesium alloy in the as-cast state and its solid solution state were investigated by means of optical microscopy (OM), scanning electron microscopy (SEM), transmission electron microscopy (TEM), electron backscatter diffraction (EBSD), X-ray diffraction (XRD), differential scanning calorimeter (DSC) and the first-principles simulation. The results show that the mechanical properties were improved after solution treatment. The CS520-12 alloy, treated at 520 °C for 12 h, exhibited excellent mechanical properties, possessing an ultimate tensile strength (UTS) of 343 ± 5 MPa and an elongation of 18.9 ± 0.8 %. These main reasons for the improving of mechanical properties was attributed the formation of I1 stacking faults (SFs) and accumulated-dislocations. The Y element, originating from the melt of the eutectic phase during solution treatment, resulted in a reduction in stacking faults energy (SFE) and facilitated the formation of I1 faults. The presence of numerous SFs hindered dislocation slip. The other key factors for elongation improving were that the weaken of texture, and geometrically necessary dislocation (GND) density decreased from 1.52 × 1013m−2 to 1.22 × 1013m−2. 14H-LPSO phase played an important role in the improving mechanical properties for CS480-12, CS480-24 and CS520-24 alloys. The higher elastic modulus of LPSO compared to Mg matrix, according to the first-principles calculated results, enabled its function as a short-fiber, thus strengthened the mechanical properties. Block-shaped 14H-LPSO in CS480-12 alloys, distributed at the grain boundaries (GBs), suppressed the grow of cracks. The lamellar 14H-LPSO within the grains of CS480-24 and CS520-24 alloys were parallel to the dislocations, which compared with SFs of CS520-12 alloy, can't effectively inhibit the movement of dislocations.

Abstract The electricity demand is increasing rapidly with the development of society and technology. Coal-fired thermal power plants have become one of the primary sources of electricity generation for urbanization. However, coal-fired thermal power plants produce a great amount of by-product coal fly ash every year. Coal fly ash disposal in landfills requires a sizable space and has negative environmental impacts. Therefore, it is crucial to develop new technologies and methods to utilize this enormous volume of solid waste in order to protect the environment. In this review, the fundamental physical and chemical characteristics of coal fly ash are introduced, and afterward the disposal policies and utilization ways of coal fly ash are discussed to gain a comprehensive understanding of the various ways this waste. The leaching of valuable metals in coal fly ash and the extraction of metal elements in leachate under different conditions are also summarized. Furthermore, the possibility of coal fly ash to serve as a supplementary source for mineral resources is analyzed, providing a basis for its extensive use as a raw material in the metal industry in China and worldwide.

Mycoplasma synoviae (MS) is an important pathogen that can cause respiratory diseases in poultry and birds, leading to serious economic losses in the world and impacting the development of the poultry industry. However, the pathogenic mechanisms of MS infection are still unclear, resulting in a lack of effective diagnosis and treatment strategies. This study aimed to uncover the infection effect caused by MS in chicken oviduct cells. MS-infected chicken oviduct cells with different infection times and doses were collected, and DAPI staining was performed to monitor the morphological changes of cell nuclei. Cell viability was detect by CCK-8 assay. The expression of marker genes of cell apoptosis was determined by RT-qPCR and Western blotting assay, respectively. The results showed that MS infection significantly inhibited the growth of chicken oviduct cells, caused the nuclear shrinkage and rupture, activated the expression of apoptosis marker genes Caspase 3 and Beclin-1, and increased the apoptosis rate. These results indicated that MS infection inhibits cell proliferation and promotes apoptosis in chicken oviduct cells, which provided a basis for further revealing the MS pathogenic mechanism and provided a foundation for the future development of anti-infection strategies.

Abstract Pulex simulans and Polygenis gwyni are vectors of many flea‐borne diseases. They were widely recorded in the United States and Mexico between 1970 and 2000. Maximum entropy models were used to explore the habitats of both fleas under different climate scenarios to provide the scientific basis for the surveillance and control of flea‐borne diseases. We screened climate variables by principal component analysis and Pearson's correlation test and evaluated model performance by ROC curve. ArcMap was used to visualize expressions. Under current climatic conditions, the medium and highly suitable areas for P. simulans are estimated to be 9.16 × 106 km2 and 4.97 × 106 km2, respectively. These regions are predominantly located in South America, along the Mediterranean coast of Europe, the southern part of the African continent, the Middle East, North China, and Australia. For P. gwyni, the medium and highly suitable areas under current climatic conditions are approximately 4.01 × 106 and 2.04 × 106 km2, respectively, with the primary distribution in North China extending to the Himalayas, near the Equator in Africa, and in a few areas of Europe. Under future climate scenarios, in the SSP3‐7.0 scenario for the years 2081–2100, the area of high suitability for P. simulans is projected to reach its maximum. Similarly, in the SSP2‐4.5 scenario for 2061–2080, the area of high suitability for P. gwyni is expected to reach its maximum. Under global climate change, there is a large range in the potential distribution for both fleas, with an overall upward trend in the area of habitat under future climate scenarios. Governments should develop scientific prevention and control measures to prevent the invasive alien species flea.

Background: Mesaconitine (MA), a diester-diterpenoid alkaloid extracted from the medicinal herb Aconitum carmichaelii, is commonly used to treat various diseases. Previous studies have indicated the potent toxicity of aconitum despite its pharmacological activities, with limited understanding of its effects on the nervous system and the underlying mechanisms.Methods: HT22 cells and zebrafish were used to investigate the neurotoxic effects of MA both in vitro and in vivo, employing multi-omics techniques to explore the potential mechanisms of toxicity.Results: Our results demonstrated that treatment with MA induces neurotoxicity in zebrafish and HT22 cells. Subsequent analysis revealed that MA induced oxidative stress, as well as structural and functional damage to mitochondria in HT22 cells, accompanied by an upregulation of mRNA and protein expression related to autophagic and lysosomal pathways. Furthermore, methylated RNA immunoprecipitation sequencing (MeRIP-seq) showed a correlation between the expression of autophagy-related genes and N6-methyladenosine (m6A) modification following MA treatment. In addition, we identified METTL14 as a potential regulator of m6A methylation in HT22 cells after exposure to MA.Conclusion: Our study has contributed to a thorough mechanistic elucidation of the neurotoxic effects caused by MA, and has provided valuable insights for optimizing the rational utilization of traditional Chinese medicine formulations containing aconitum in clinical practice.

BackgroundHemorrhagic Fever with Renal Syndrome (HFRS) continues to pose a significant public health threat to the well-being of the population. Given that the spread of HFRS is susceptible to meteorological factors, we aim to probe into the meteorological drivers of HFRS. Thus, novel techniques that can discern time-delayed non-linear relationships from nonlinear dynamical systems are compulsory.MethodsWe analyze the epidemiological features of HFRS in Weifang City, 2011-2020, via the employment of the Empirical Dynamic Modeling (EDM) method. Our analysis delves into the intricate web of time-delayed non-linear associations between meteorological factors and HFRS. Additionally, we investigate the repercussions of minor perturbations in meteorological variables on future HFRS incidence.ResultsA total of 2515 HFRS cases were reported in Weifang from 2011 to 2020. The number of cases per week was 4.81, and the average weekly incidence was 0.52 per 1,000,000. The propagation of HFRS is significantly impacted by the mean weekly temperature, relative humidity, cumulative rainfall, and wind speed, and the ρCCM converges to 0.55,0.48,0.38 and 0.39, respectively. The graphical representation of the relationship between temperature (lagged by 2 weeks) and the incidence of HFRS exhibits an inverted U-shaped curve, whereby the incidence of HFRS culminates as the temperature reaches 10 °C. Moreover, temperature, relative humidity, cumulative rainfall, and wind speed exhibit a positive correlation with HFRS incidence, with a time lag of 4-6 months.ConclusionsOur discoveries suggest that meteorological factors can drive the transmission of HFRS both at a macroscopic and microscopic scale. Prospective alterations in meteorological conditions, for instance, elevations in temperature, relative humidity, and precipitation will instigate an upsurge in the incidence of HFRS after 4-6 months, and thus, timely public health measures should be taken to mitigate these changes.

Abstract Background Human health is seriously threatened by antibiotic-induced intestinal disorders. Herein, we aimed to determine the effects of Autoinducer-2 (AI-2) combined with Lactobacillus rhamnosus GG (LGG) on the intestinal barrier function of antibiotic-induced intestinal dysbiosis neonatal mice. Methods An antibiotic-induced intestinal dysbiosis neonatal mouse model was created using antibiotic cocktails, and the model mice were randomized into the control, AI-2, LGG, and LGG + AI-2 groups. Intestinal short-chain fatty acids and AI-2 concentrations were detected by mass spectrometry and chemiluminescence, respectively. The community composition of the gut microbiota was analyzed using 16S rDNA sequencing, and biofilm thickness and bacterial adhesion in the colon were assessed using scanning electron microscopy. Transcriptome RNA sequencing of intestinal tissues was performed, and the mRNA and protein levels of HCAR2 (hydroxycarboxylic acid receptor 2), claudin3, and claudin4 in intestinal tissues were determined using quantitative real-time reverse transcription PCR and western blotting. The levels of inflammatory factors in intestinal tissues were evaluated using enzyme-linked immunosorbent assays (ELISAs). D-ribose, an inhibitor of AI-2, was used to treat Caco-2 cells in vitro. Results Compared with the control, AI-2, and LGG groups, the LGG + AI-2 group showed increased levels of intestinal AI-2 and proportions of Firmicutes and Lacticaseibacillus, but a reduced fraction of Proteobacteria. Specifically, the LGG + AI-2 group had considerably more biofilms and LGG on the colon surface than those of other three groups. Meanwhile, the combination of AI-2 and LGG markedly increased the concentration of butyric acid and promoted Hcar2, claudin3 and claudin4 expression levels compared with supplementation with LGG or AI-2 alone. The ELISAs revealed a significantly higher tumor necrosis factor alpha (TNF-α) level in the control group than in the LGG and LGG + AI-2 groups, whereas the interleukin 10 (IL-10) level was significantly higher in the LGG + AI-2 group than in the other three groups. In vitro, D-ribose treatment dramatically suppressed the increased levels of Hcar2, claudin3, and claudin4 in Caco-2 cells induced by AI-2 + LGG. Conclusions AI-2 promotes the colonization of LGG and biofilm formation to improve intestinal barrier function in an antibiotic-induced intestinal dysbiosis neonatal mouse model.

Abstract Background Attention provides the foundation for cognitions, which was shown to be affected by microwave (MW) radiation. With the ubiquitous of microwaves, public concerns regarding the impact of MW radiation on attention has hence been increased. Our study aims to investigate the potential effect and mechanism of acute microwave exposure on attention. Results We identified obvious impairment of attention in mice by the five-choice serial reaction time (5-CSRT) task. Proteomic analysis of the cerebrospinal fluid (CSF) revealed neuroinflammation and microglial activation potentially due to acute MW exposure. Moreover, biochemical analysis further confirmed microglial activation in the prefrontal cortex (PFC) of mice subjected to acute MW exposure. Finally, minocycline, a commercially available anti-inflammatory compound, attenuated neuroinflammation, inhibited the upregulation of N-methyl-D-aspartic acid receptor (NMDAR) including NR2A and NR2B, and also accelerated the attentional recovery after MW exposure. Conclusions We believe that microglial activation and NMDAR upregulation likely contribute to inattention induced by acute MW exposure, and we found that minocycline may be effective in preventing such process.

Abstract Objective This study aimed to explore the characteristics of carbapenem-resistant Enterobacterales (CRE) patients in the intensive care unit (ICU) in different regions of Henan Province to provide evidence for the targeted prevention and treatment of CRE. Methods This was a cross-sectional study. CRE screening was conducted in the ICUs of 78 hospitals in Henan Province, China, on March 10, 2021. The patients were divided into provincial capital hospitals and nonprovincial capital hospitals for comparative analysis. Results This study involved 1009 patients in total, of whom 241 were CRE-positive patients, 92 were in the provincial capital hospital and 149 were in the nonprovincial capital hospital. Provincial capital hospitals had a higher rate of CRE positivity, and there was a significant difference in the rate of CRE positivity between the two groups. The body temperature; immunosuppressed state; transfer from the ICU to other hospitals; and use of enemas, arterial catheters, carbapenems, or tigecycline at the provincial capital hospital were greater than those at the nonprovincial capital hospital (P

Abstract Our previous work demonstrated the tendon-derived extracellular matrix (ECM) extracts as vital niches to specifically direct mesenchymal stem cells towards tenogenic differentiation. This study aims to further define the effective ECM molecules capable of teno-lineage induction on human adipose-derived stem cells (hASCs) and test their function for tendon engineering. By detecting the teno-markers expression levels in hASCs exposed to various substrate coatings, collagen I (COL1) and fibromodulin (FMOD) were identified to be the key molecules as a combination and further employed to the modification of poly(L-lactide-co-ε-caprolactone) electrospun nanoyarns, which showed advantages in inducting seeded hASCs for teno-lineage specific differentiation. Under dynamic mechanical loading, modified scaffold seeded with hASCs formed neo-tendon in vitro at the histological level and formed better tendon tissue in vivo with mature histology and enhanced mechanical properties. Primary mechanistic investigation with RNA sequencing demonstrated that the inductive mechanism of these two molecules for hASCs tenogenic differentiation was directly correlated with positive regulation of peptidase activity, regulation of cell-substrate adhesion and regulation of cytoskeletal organization. These biological processes were potentially affected by LOC101929398/has-miR-197-3p/TENM4 ceRNA regulation axis. In summary, COL1 and FMOD in combination are the major bioactive molecules in tendon ECM for likely directing tenogenic phenotype of hASCs and certainly valuable for hASCs-based tendon engineering.

Citri Reticulatae Pericarpium (CRP), particularly including the pericarp of Citrus reticulata ‘Chachi’ (GCP), has been widely used as a food, a dietary supplement, and traditional Chinese medicine. Despite the widespread use of traditional foods, there is limited evidence regarding the precise relationships between storage conditions, aging duration, and the digestive performance of CRP. In this study, the aim was to investigate the impact of the storage conditions on the quality of aged GCP during shelf life and to evaluate the subsequent digestive performance of corresponding GCP decoctions. Respiration in GCP was monitored by measuring oxygen (O2), carbon dioxide (CO2), and methane (CH4) gases throughout the storage simulation, with O2 and CO2 validated as prospective safety measures. Five flavonoids (hesperidin, didymin, nobiletin, tangeretin, and 3,5,6,7,8,3′,4′-heptamethoxyflavone) were determined as quality indicators, and their contents were significantly affected by the duration of the storage simulation and the aging periods of GCP. Our study also found that temperature and humidity significantly affected the volatile organic compounds (VOCs) emission from GCP. Eighteen compounds were proposed to show potential as descriptive measures of aging periods while eight compounds were proposed as potential indicators to discriminate among the spoilage level. Furthermore, the bioaccessibility of hesperidin ranged from ~30% to ~50% and was not significantly affected by the GCP’s aging time nor the consumer’s sex (p < 0.05). This study presents evidence for the future control of the quality of GCP and its digestive performance in males and females.

Fusarium pseudograminearum (Fpg) is a significant pathogen responsible for fusarium crown rot (FCR) in wheat (Triticum aestivum L.), a disease with devastating impacts on crop yield. The utilization of biocontrol bacteria to combat fungal diseases in plants is a cost-effective, eco-friendly, and sustainable strategy. In this trial, an endophytic bacterial species, designated as SW, was isolated from the roots of wheat. The strain exhibited potent antagonistic effects against Fpg and reduced the FCR disease severity index by 76.07 ± 0.33% in a greenhouse pot trial. Here, 106 colony-forming units (CFUs)/mL of the SW strain was determined to be the minimum dose required to exhibit the antagonism against Fpg. The strain was identified as Bacillus atrophaeus using genome sequencing and comparison with type strains in the NCBI database. Whole-genome sequencing analysis revealed that SW harbors genes for siderophores, antifungal metabolites, and antibiotics, which are key contributors to its antagonistic activity. Additionally, the strain’s ability to utilize various carbon and nitrogen sources, successfully colonize wheat root tissues as an endophyte, and form biofilms are critical attributes for promoting plant growth. In summary, these findings demonstrate the ability of Bacillus atrophaeus to control FCR disease in wheat in a sustainable agricultural setting.

The study describes large strain high-speed asynchronous rolling process to process AZ91 magnesium alloy sheets with an overall thickness reduction of 84 % via two-pass rolling at 350 °C. Rolling speed ratios of 1.0, 1.1, 1.2, and 1.3 were used to obtain bimodal grain structure with different organizational states. Microstructural analysis unraveled that the formation of the bimodal structure was a consequence of combined effect of precipitation-strengthening and the Zener pinning effect. The R3 exhibiting an asynchronous ratio of 1.2 exhibited an optimized bimodal grain structure characterized by smaller recrystallized grains and a more homogeneous distribution. This phenomenon underscored the beneficial impact on enhancing strength and alleviating the anisotropic behavior.

Abstract Hypoxic-ischemic encephalopathy (HIE) at high-altitudes leads to neonatal mortality and long-term neurological complications without effective treatment. Acer truncatum Bunge Seed extract (ASO) is reported to have effect on cognitive improvement, but its molecular mechanisms on HIE are unclear. In this study, ASO administration contributed to reduced neuronal cell edema and improved motor ability in HIE rats at a simulated 4500-meter altitude. Transcriptomics and WGCNA analysis showed genes associated with lipid biosynthesis, redox homeostasis, neuronal growth, and synaptic plasticity regulated in the ASO group. Targeted and untargeted-lipidomics revealed decreased free fatty acids and increased phospholipids with favorable ω-3/ω-6/ω-9 fatty acid ratios, as well as reduced oxidized glycerophospholipids (OxGPs) in the ASO group. Combining multi-omics analysis demonstrated FA to FA-CoA, phospholipids metabolism, and lipid peroxidation were regulated by ASO treatment. Our results illuminated preliminary metabolism mechanism of ASO ingesting in rats, implying ASO administration as potential intervention strategy for HIE under high-altitude.

Abstract The SHI RELATED SEQUENCE (SRS) family plays a vital role in the development of multiple plant organs such as floral meristem determinacy, organ morphogenesis, and signal transduction. Nevertheless, there is little understanding of the biological significance of tomato SRS family at this point. Our research identified eight SlSRS family members and classified them into three subfamilies based on phylogenetics, conserved motifs, and characteristic domain analysis. The intraspecies and interspecies collinearity analysis revealed clues of SRS family evolution. Many cis-elements related to hormones, stresses, and plant development can be found in the promoter region of SlSRS genes. All of eight SlSRS proteins were located in the nucleus and possessed transcriptional activity, half of which were transcriptional activators, and the other half were transcriptional repressors. Except for SlSRS1, which showed high transcript accumulation in vegetative organs, most SlSRS genes expressed ubiquitously in all flower organs. In addition, all SlSRS genes could significantly respond to at least four different plant hormones. Further, expression of SlSRS genes were regulated by various abiotic stress conditions. In summary, we systematically analyzed and characterized the SlSRS family, reviewed the expression patterns and preliminarily investigated the protein function, and provided essential information for further functional research of the tomato SRS genes in the determination of reproductive floral organs and the development of plants, and possibly other plants.

Flower and fruit abscission is a highly programmed physiological process, which is closely related to the yield of horticultural plants. The coordination of many regulatory factors associated with metabolic and signaling pathways plays a key role in the flower and fruit shedding. Hormones, peptides, carbohydrates, polyamines or cell wall modifying proteins regulate flower and fruit shedding. This article reviewed the recent studies of flower and fruit abscission, including the molecular regulation mechanism of abscission zone formation, typical structure and location of abscission zones, and other factors affecting flower and fruit abscission, such as stresses, hormones, peptides, carbohydrates, polyamines and cell wall modifying proteins. Overall, the review summarizes the developmental mechanism and the diversity of abscission zones, and the key factors affecting flower and fruit abscission of horticultural plants, aiming to provide guidance for studying the molecular regulatory mechanism of flower and fruit abscission.

Molecular dynamics (MD) simulation and experiments were carried out in this work to probe the microstructure evolution in the semi-solid compression (SSC) of AZ80 magnesium alloy. The liquid phase flow, stress fluctuations, grain refinement, dislocation generation, and texture evolution were discussed. Results indicate that the liquid phase was squeezed out along the radial direction prior the solid phase at the beginning of compression. Stress-strain curve represented obvious fluctuation at lower strain rates. That resulted from stress reduction caused by more liquid evolving with a lower strain rate at an elevated temperature. Plastic deformation was detected in grains and the dislocations of 1/3 dominated the deformation, while and 1/3 just been activated at the beginning of SSC process. The results of EBSD showed the grains size was refined into about 38.8 μm from 92.3 μm after SSC process. During the process, grain refinement resulted in the increase of low-angle grain boundaries (LAGBs), and a strong (0001) basal plane texture evolved at the end. The higher the strain rates, the stronger the texture.

Although anti-TNF antibodies are extensively used to treat Crohn's disease (CD), a significant proportion of patients, up to 40%, exhibit an inadequate response to this therapy. Our objective was to identify potential targets that could improve the effectiveness of anti-TNF therapy in CD. Through the integration and analysis of transcriptomic data from various CD databases, we found that the expression of AQP9 was significantly increased in anti-TNF therapy-resistant specimens. The response to anti-TNF therapy in the CD mouse model was significantly enhanced by specifically inhibiting AQP9. Further experiments found that the blockade of AQP9, which is dominantly expressed in macrophages, decreased inflamed macrophage functions and cytokine expression. Mechanistic studies revealed that AQP9 transported glycerol into macrophages, where it was metabolized to LPA, which was further metabolized to LPA, resulting in the activation of the LPAR2 receptor and downstream hippo pathway, finally promoting the expression of cytokines, especially IL23 and IL1β⊡ Taken together, the expansion of AQP9+ macrophages is associated with resistance to anti-TNF therapy in Crohn’s disease. These findings indicated that AQP9 could be a potential target for enhancing anti-TNF therapy in Crohn’s disease.

BackgroundIn previous investigations, we explored the regulation of gastric function by hydrogen sulfide (H2S) and L-glutamate (L-Glu) injections in the nucleus ambiguus (NA). We also determined that both H2S and L-Glu have roles to play in the physiological activities of the body, and that NA is an important nucleus for receiving visceral sensations. The purpose of this study was to explore the potential pathway link between L-Glu and H2S, resulting in the regulation of gastric function.MethodsPhysiological saline (PS), L-glutamate (L-Glu, 2 nmol), NaHS (2 nmol), D-2-amino-5-phopho-novalerate (D-AP5, 2 nmol) + L-Glu (2 nmol), aminooxyacetic acid (AOAA, 2 nmol) + L-Glu (2 nmol), D-AP5 (2 nmol) + NaHS (2 nmol) were injected into the NA. A balloon was inserted into the stomach to observe gastric pressure and for recording the changes of gastric smooth muscle contraction curve. The gastric fluid was collected by esophageal perfusion and for recording the change of gastric pH value.ResultsInjecting L-Glu in NA was found to significantly inhibit gastric motility and promote gastric acid secretion in rats (p < 0.01). On the other hand, injecting the PS, pre-injection N-methyl-D-aspartate (NMDA) receptor blocker D-AP5, cystathionine beta-synthase (CBS) inhibitor AOAA and re-injection L-Glu did not result in significant changes (p > 0.05). The same injection NaHS significantly inhibit gastric motility and promote gastric acid secretion in rats (p < 0.01), but is eliminated by injection D-AP5 (p > 0.05).ConclusionThe results indicate that both exogenous L-Glu and H2S injected in NA regulate gastric motility and gastric acid secretion through NMDA receptors. This suggests that NA has an L-Glu-NMDA receptor-CBS-H2S pathway that regulates gastric function.

Abstract RNA modification, especially RNA methylation, is a critical posttranscriptional process influencing cellular functions and disease progression, accounting for over 60% of all RNA modifications. It plays a significant role in RNA metabolism, affecting RNA processing, stability, and translation, thereby modulating gene expression and cell functions essential for proliferation, survival, and metastasis. Increasing studies have revealed the disruption in RNA metabolism mediated by RNA methylation has been implicated in various aspects of cancer progression, particularly in metabolic reprogramming and immunity. This disruption of RNA methylation has profound implications for tumor growth, metastasis, and therapy response. Herein, we elucidate the fundamental characteristics of RNA methylation and their impact on RNA metabolism and gene expression. We highlight the intricate relationship between RNA methylation, cancer metabolic reprogramming, and immunity, using the well‐characterized phenomenon of cancer metabolic reprogramming as a framework to discuss RNA methylation's specific roles and mechanisms in cancer progression. Furthermore, we explore the potential of targeting RNA methylation regulators as a novel approach for cancer therapy. By underscoring the complex mechanisms by which RNA methylation contributes to cancer progression, this review provides a foundation for developing new prognostic markers and therapeutic strategies aimed at modulating RNA methylation in cancer treatment.

To enhance the temperature control capability of photovoltaic-phase change material systems, a strategy involving the combination of fins and partitioned cavities is employed to enhance the heat transfer process. Thermal performance of four cavity arrangements including a rectangular cavity, a partitioned rectangular cavity, a finned rectangular cavity, and a partitioned rectangular cavity with fins at two tilt angles of 90° and 45° are numerically evaluated. By employing a partitioned cavity with fins, the entire melting time can be reduced by a maximum of 8.9% compared to the baseline case. Moreover, the results show that the individual or simultaneous utilization of the partition and fins at an inclination angle of 90° can not only effectively reduce PV panel temperature but also improve temperature uniformity of the PV panel. Reducing the inclination angle to 45° prolongs the melting time, and this also reduces the temperature control performance for the majority cavity structures. Compared with the baseline case, the temperature of the PV panel can be reduced by up to 5.0 K, and the temperature uniformity can be increased by a maximum of 35.0%. The partitioned cavity coupled with fins has the best overall thermal performance among all structures.

Abstract This study aimed to visualize the knowledge structure and research trends in neonatal sepsis research through bibliometric methods. Articles and reviews regarding neonatal sepsis from 2002 to 2022 were retrieved from the Web of Science Core Collection database. CiteSpace software was used to visualize the knowledge network of countries/regions, institutions, authors, journals, keywords, and references in this field. Altogether, 2314 publications were identified. During the study period, the number of publications increased yearly. The USA is the leading country in neonatal sepsis research. Duke University was the most prolific institution, with Pediatric Infectious Disease Journal and BASU S being the most prolific journal and author in the field, respectively. Pathogen, diagnosis, and management were the main topics of research, and future studies may concentrate on novel diagnostic biomarkers and judicious use of antibiotics. In summary, the results of our bibliometric analysis revealed views on the current situation and trends of neonatal sepsis research for the first time. This study may provide guidance for promoting research on neonatal sepsis.

Background: This study aimed to identify the specific areas of knowledge gaps regarding lactose intolerance among neonatologists in Chinese outpatient settings as well as to assess the availability of lactose intolerance testing in hospitals. Methods: A total of 278 neonatologists in outpatient settings from 144 hospitals were surveyed. To explore the awareness level, diagnosis, and treatment of neonatal lactose intolerance among neonatologists in outpatient settings, a multicenter cross-sectional survey was designed. Descriptive analysis based on frequency and percent distribution was performed for all variables. Results: Most respondents were senior doctors (256, 92.09%) from general hospitals and maternity/maternal and child health hospitals, had over 10 years of experience, and were dominantly associate chief physicians and chief physicians (211, 75.90%). A significant proportion of the participants (236, 84.89%) believed that neonatal lactose intolerance tends to be overlooked during clinical practice. When the most common symptoms of neonatal lactose intolerance were surveyed, diarrhea was selected by 142 (51.08%) respondents, followed by bloating and milk regurgitation or emesis (71, 25.54%). Other symptoms included unexplained crying (36, 12.85%), stool with milk flap or foam (15, 5.40%), and increased venting (14, 5.04%). Furthermore, the survey results indicated that the most common method for diagnosing neonatal lactose intolerance in the respondents’ hospitals was qualitative test for urinary galactose (78, 28.06%). Of the respondents, 137 (49.28%) stated that their hospital could not test for lactose intolerance. For treating lactose intolerance, the neonatologists primarily opted for exogenous lactase rather than lactose-free formula milk. Conclusions: This study sheds light on Chinese neonatologists’ awareness of neonatal lactose intolerance, revealing some knowledge gaps. The expeditious popularization and conduct of lactose intolerance-related examinations in hospitals will have a positive stimulative effect on the management of lactose intolerance in newborns.

Loop closure detection is crucial for simultaneous localization and mapping (SLAM), as it can effectively correct the accumulated errors. Complex scenarios put forward high requirements on the robustness of loop closure detection. Traditional feature-based loop closure detection methods often fail to meet these challenges. To solve this problem, this paper proposes a robust and efficient deep-learning-based loop closure detection approach. We employ MixVPR to extract global descriptors from keyframes and construct a global descriptor database. For local feature extraction, SuperPoint is utilized. Then, the constructed global descriptor database is used to find the loop frame candidates, and LightGlue is subsequently used to match the most similar loop frame and current keyframe with the local features. After matching, the relative pose can be computed. Our approach is first evaluated on several public datasets, and the results prove that our approach is highly robust to complex environments. The proposed approach is further validated on a real-world dataset collected by a drone and achieves accurate performance and shows good robustness in challenging conditions. Additionally, an analysis of time and memory costs is also conducted and proves that our approach can maintain accuracy and have satisfactory real-time performance as well.

Objective: The influence of maternal smoking around birth (MSAB) on offspring allergic diseases, specifically childhood asthma (CA), allergic rhinitis (AR), allergic conjunctivitis (AC), and atopic dermatitis (AD) remains incompletely understood. We performed a rigorous mendelian randomization (MR) study to obtain the unconfounded association between MSAB and allergic diseases in offspring with and without adjustment for the effect of breastfeeding. Methods: Utilizing publicly available information of MSAB, breastfeeding, CA, AR, AC, and AD from large-scale genome-wide association studies (GWAS), we performed a two-sample mendelian randomization (TSMR) analysis to assess the respective causal relationship of MSAB and breastfeeding to allergic diseases in offspring. To get a reliable conclusion, MR Egger regression, weighted median, and inverse variance weighted (IVW) were employed to estimate the causality, with IVW as the primary analysis. Multivariate MR (MVMR) analysis was used to assess the effect of MSAB on allergic diseases after adjusting for breastfeeding's impact. Sensitivity analysis was conducted using the Cochran Q test, MR-Egger, and leave-one-out approaches to ensure the reliability and stability of results. Results: The TSMR analysis demonstrated MSAB increased the risks of CA (PIVW = 0.013, OR: 1.018, 95%CI: 1.004 to 1.033) and AD (PIVW = 0.006, OR: 8.293, 95%CI: 1.815 to 37.884) in offspring. Conversely, breastfeeding decreased the risk of CA (PIVW

In mammals, the transcription factor Pax5 is a key regulator of B cell development and maturation and specifically expressed in naive/mature B cells but repressed upon B cell activation. Despite the long-standing proposal that Pax5 repression is essential for proper B cell activation, the underlying mechanisms remain largely elusive. In this study, we used a teleost model to elucidate the mechanisms governing Pax5 repression during B cell activation. Treatment with lipopolysaccharide (LPS) and chitosan oligosaccharide (COS) significantly enhanced the antibody secreting ability and phagocytic capacity of IgM+ B cells in large yellow croaker (Larimichthys crocea), coinciding with upregulated expression of activation-related genes, such as Bcl6, Blimp1, and sIgM, and downregulated expression of Pax5. Intriguingly, two CpG islands were identified within the promoter region of Pax5. Both CpG islands exhibited hypomethylation in naive/mature B cells, while CpG island1 was specifically transited into hypermethylation upon B cell activation. Furthermore, treatment with DNA methylation inhibitor 5-aza-2’-deoxycytidine (AZA) prevented the hypermethylation of CpG island1, and concomitantly impaired the downregulation of Pax5 and activation of B cells. Finally, through in vitro methylation experiments, we demonstrated that DNA methylation exerts an inhibitory effect on promoter activities of Pax5. Taken together, our findings unveil a novel mechanism underlying Pax5 repression during B cell activation, thus promoting the understanding of B cell activation process.

Aims The objective of this study is to examine the impact of inhibiting Sphingosine 1-phosphate receptor 2 (S1PR2) on liver inflammation, fibrogenesis, and changes of gut microbiome in the context of cholestasis-induced conditions. Methods The cholestatic liver injury model was developed by common bile duct ligation (CBDL). Sprague-Dawley rats were randomly allocated to three groups, sham operation, CBDL group and JTE-013 treated CBDL group. Biochemical and histological assessments were conducted to investigate the influence of S1PR2 on the modulation of fibrogenic factors and inflammatory infiltration. We conducted an analysis of the fecal microbiome by using 16S rRNA sequencing. Serum bile acid composition was evaluated through the utilization of liquid chromatography-mass spectrometry techniques. Results In the BDL rat model, the study findings revealed a significant increase in serum levels of conjugated bile acids, accompanied by an overexpression of S1PR2. Treatment with the specific inhibitor of S1PR2, known as JTE-013, resulted in a range of specific effects on the BDL rats. These effects included the improvement of liver function, reduction of liver inflammation, inhibition of hepatocyte apoptosis, and suppression of NETosis. These effects are likely mediated through the TCA/S1PR2/NOX2/NLRP3 pathway. Furthermore, the administration of JTE-013 resulted in an augmentation of the diversity of the bacterial community’s diversity, facilitating the proliferation of advantageous species while concurrently inhibiting the prevalence of detrimental bacteria. Conclusions The results of our study suggest that the administration of JTE-013 may have a beneficial effect in alleviating cholestatic liver disease and restoring the balance of intestinal flora.

To evaluate the effectiveness and safety of respiratory syncytial virus (RSV) vaccination during pregnancy in preventing lower respiratory tract infection (LRTI) in infants and neonates, we conducted a systematic search of randomized controlled trials (RCTs) in five databases (PubMed, Embase and Cochrane Library, Web of Science, Cochrane Center Register of Controlled trial) until 1 May 2023. We performed a meta-analysis of the eligible trials using RevMan5.4.1 software. Our analysis included six articles and five RCTs. The meta-analysis revealed significant differences in the incidences of LRTI [risk ratio (RR): 0.64; 95% confidence interval (CI): 0.43, 0.96; p = 0.03)] and severe LRTI (RR: 0.37; 95% CI: 0.18, 0.79; p = 0.01) between the vaccine group and the placebo group for newborns and infants. These differences were observed at 90, 120, and 150 days after birth (p = 0.003, p = 0.05, p = 0.02, p = 0.03, p = 0.009, p = 0.05). At 180 days after birth, there was a significant difference observed in the incidence of LRTI between the two groups (RR: 0.43; 95% CI: 0.21, 0.90; p = 0.02). The safety results showed a significant difference in the incidence of common adverse events between the two groups (RR: 1.08; 95% CI: 1.04, 1.12; p

Former meta-analyses concluded that there was not sufficient evidence to determine the effect of surgical masks and N95 respirators. We collected randomized controlled trials (RCTs) and conducted a systematic review and meta-analysis to evaluate the efficacy of N95 respirators and surgical masks for protection against COVID-19. We retrieved relevant RCTs published between January 2019 and January 2023 by searching the PubMed, EMBASE, and Cochrane CENTRAL. Study quality was evaluated using the Cochrane Risk of Bias tool with the RevMan 5.4 software. Meta-analyses were conducted to calculate pooled estimates using the RevMan 5.4 software. A total of six RCTs were finally included. The findings revealed that wearing a mark made little difference in preventing COVID-19 [odds ratio (OR) = 0.10; 95% confidence interval (CI): 0.01–0.93; P = 0.04]. Subgroup analysis showed that the heterogeneity of data was I2 = 64% (OR = 0.32; 95% CI: 0.06–1.77; P = 0.19) for surgical mask use and I2 = 0% (OR = 0.03; 95 %CI: 0.01–0.15; P

Background: Current evidence shows that systemic dexamethasone administration starting after the first week of age reduces bronchopulmonary dysplasia for very preterm (VPT) infants, but its neurological effects remain obscure. Using resting-state functional magnetic resonance imaging (rs-fMRI), we assessed the changes in functional network connectivity (FNC) in very preterm infants treated with late systemic dexamethasone (≥7 days of age). Methods: VPT infants (GA ≤ 32 weeks) who needed to rely on mechanical ventilation for more than 7 days but fewer than 14 days to maintain vital signs were included in the study. The cohort was divided into two groups according to whether they were given systemic dexamethasone. In addition, 26 healthy term infants were recruited as controls. At term-equivalent age (TEA), rs-fMRI and 3D-T1 data from eligible infants were acquired with a 3.0-T MRI scanner. After the MRI data were preprocessed, group-level independent component analysis (ICA), a technique used for blind source separation, was used to identify the components of resting-state networks (RSNs). Then, the functional connectivity between components and RSNs was compared among different groups. Upon follow-up at 3 months of corrected age, the neurodevelopmental outcomes of enrolled infants were assessed with the Bayley Scales of Infant Development–Chinese Revision (BSID-CR), and the Motor Development Index (MDI) and Psychomotor Development Index (PDI) were measured. Finally, the correlations between resting-state FNC and BSID scores were analysed. Results: Ultimately, 59 infants were included in the final analysis, including 19 preterm infants who received dexamethasone, 20 who did not, and 20 healthy term infants as controls. Based on their data, 11 components were identified, belonging to 5 RSNs: the visual network (VN), the dorsal attention network (DAN), the auditory network (AN), the primary sensorimotor network (SMN), and the default-mode network (DMN). Compared with the term infants, the preterm infants showed significantly weakened functional connectivity between the DAN and VN, as well as the VN and AN (P

Highlights Microglial activation influences metabolic connectivity. Microglial depletion results in distinct decreases of metabolic connectivity. Metabolic connectivity increases in progranulin deficient mice. Cellular FDG allocation in progranulin deficient mice is shifted to microglia.

Elongation factor Tu GTP binding domain protein 2 (Eftud2) is a spliceosomal GTPase that serves as an innate immune modulator restricting virus infection. Microglia are the resident innate immune cells and the key players of immune response in the central nervous system. However, the role of Eftud2 in microglia has not been reported. In this study, we performed immunofluorescent staining and western blot assay and found that Eftud2 was upregulated in microglia of a 5xFAD transgenic mouse model of Alzheimer’s disease. Next, we generated an inducible microglia-specific Eftud2 conditional knockout mouse line (CX3CR1-CreER; Eftud2f/f cKO) via Cre/loxP recombination and found that Eftud2 deficiency resulted in abnormal proliferation and promoted anti-inflammatory phenotype activation of microglia. Furthermore, we knocked down Eftud2 in BV2 microglia with siRNA specifically targeting Eftud2 and found that Eftud2-mediated regulation of microglial proinflammatory/anti-inflammatory phenotype activation in response to inflammation might be dependent on the NF-κB signaling pathway. Our findings suggest that Eftud2 plays a key role in regulating microglial polarization and homeostasis possibly through the NF-κB signaling pathway.

Abstract Background Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease with high morbidity and mortality, affecting preterm infants especially those with very low and extremely low birth weight. β-glucan has manifested multiple biological effects including anti-inflammatory, regulation of gut microbiota, and immunomodulatory activities. This study aimed to investigate the effects of β-glucan on NEC. Methods Neonatal C57BL/6 mice were randomly divided into three groups: Control group, NEC group and β-glucan group. Newborn 3-day-old mice were gavaged with either 1 mg/ml β-glucan or phosphate buffer saline at 0.03 ml/g for 7 consecutive days before NEC induction and a NEC model was established with hypoxia combined with cold exposure and formula feeding. All the pups were killed after 72-h modeling. Hematoxylin–eosin staining was performed to assess the pathological injury to the intestines. The mRNA expression levels of inflammatory factors in intestinal tissues were determined using quantitative real-time PCR. The protein levels of TLR4, NF-κB and tight junction proteins in intestinal tissues were evaluated using western blotting and immunohistochemistry. 16S rRNA sequencing was performed to determine the structure of the gut microbiota. Results β-glucan administration ameliorated intestinal injury of NEC mice; reduced the intestinal expression of TLR4, NF-κB, IL-1β, IL-6, and TNF-α; increased the intestinal expression of IL-10; and improved the expression of ZO-1, Occludin and Claudin-1 within the intestinal barrier. Pre-treatment with β-glucan also increased the proportion of Actinobacteria, Clostridium butyricum, Lactobacillus johnsonii, Lactobacillus murinus, and Lachnospiraceae bacterium mt14 and reduced the proportion of Klebsiella oxytoca g Klebsiella in the NEC model. Conclusion β-glucan intervention prevents against NEC in neonatal mice, possibly by suppressing the TLR4-NF-κB signaling pathway, improving intestinal barrier function, and partially regulating intestinal microbiota.

Abstract Background Dural arteriovenous fistulas (DAVF) represent almost 10–15% of intracranial malformations that cause intracranial hemorrhage and focal neurological deficits. Seldom tentorial DAVF cases present with ocular manifestations initially, which occur frequently in carotid–cavernous fistula (CCF) and cavernous sinus DAVF (CS DAVF). Case presentation We report an unusual falcotentorial DAVF case draining via the superior and inferior ophthalmic veins that caused left-side increased intraocular pressure. The patient’s chief complaint was swelling on the left side, pain and conjunctival congestion. He received endovascular embolization via a transarterial approach, and postoperative angiography demonstrated that the falcotentorial DAVF was occluded completely. Conclusion Except for CCF and CS DAVF, some specific subtypes of DAVF should be considered if the patient initially presents with ocular symptoms. Differential diagnosis and definitive treatment are mandatory to avoid a delayed diagnosis and irreversible symptoms.